A Study to Investigate APL-4098 Alone and/or in Combination With Azacitidine in R/R AML and High-Risk MDS

Acute Myeloid Leukemia, in Relapse Clinical Trial

Official title:

A Phase 1/2 Study to Assess the Safety and Antitumor Activity of APL-4098 Alone and/or in Combination With Azacitidine in Adults With Relapsed or Refractory (R/R) Acute Myeloid Leukemia (AML), Myelodysplastic Syndrome/AML (MDS/AML) or Myelodysplastic Syndrome With Excess Blasts (MDS-EB)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06372717
• Other study ID #: AP30CP01
• Status: Not yet recruiting
• Phase: Phase 1/Phase 2
• Start date: April 2024
• Est. completion date: April 1, 2027

Study information

• Verified date: April 2024
• Source: Apollo Therapeutics Ltd
• Contact: Apollo Therapeutics
• Phone: 781-479-2267
• Email: AP30[@]apollotx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is an open-label, Phase 1/2 study to determine the safety, tolerability, and efficacy of APL-4098 alone and/or in combination with azacitidine for the treatment of relapsed or refractory (R/R) acute myeloid leukemia (AML), myelodysplastic syndrome (MDS)/AML and MDS-excess blasts (EB). Participants with the MDS-EB subtype will be eligible for the Phase 1 part of the study only.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 112
• Est. completion date: April 1, 2027
• Est. primary completion date: March 1, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 18 years or older

• Confirmed diagnosis of relapsed refractory acute myeloid leukemia (R/R AML), myelodysplastic syndrome (MDS)/ AML, or MDS-excess blasts (MDS-EB) with the following characteristics: - R/R AML (primary or secondary, including treatment-related), participant is intolerant to, or considered ineligible for available therapies known to provide clinical benefit.

• WBC count = 25,000/microliter

• ECOG Performance Status of = 2

• Weight = 40kg

• Female participants of childbearing potential must have negative serum pregnancy test at screening; must not plan to become pregnant or have ova harvested or breastfeed while on study; must we willing to use specific contraception or avoid intercourse

• Male participants must be willing to use specific contraception and not plan to impregnant a female partner or donate sperm while on study

• Participant must be willing and able to provide written informed consent and to comply with the requirements of the trial

Exclusion Criteria:

• Certain prior therapies such as: received an allogeneic stem cell transplant within 6 months of screening, received an autologous stem cell transplant within 3 months of screening, received any anti-cancer treatments within 2 weeks of Cycle 1 Day 1, prior radiation therapy within 4 weeks of screening

• Certain medical conditions such as: other malignancies, myocardial infarction within 6 months of screening, symptomatic congestive heart failure, uncontrolled active infection, history of arterial thrombosis within 6 months of screening

• Diagnostic assessments: Left ventricular ejection fraction < 45%, Fridericia's corrected QT interval > 470msec, Aspartate aminotransferase and/or alanine aminotransferase > 3 x upper limit of normal (ULN), total bilirubin > 1.5 x ULN, calculated or measured creatinine clearance < 45 mL/minute (multiply by 0.85 if female)

• Infectious disease: HIV positive, active hepatitis B and/or C

Related Conditions & MeSH terms

• Acute Myeloid Leukemia Refractory
• Acute Myeloid Leukemia, in Relapse
• Anemia, Refractory, with Excess of Blasts
• GATA2 Deficiency
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Myelodysplastic Syndrome Acute Myeloid Leukemia
• Myelodysplastic Syndrome With Excess Blasts
• Myelodysplastic Syndromes
• Preleukemia
• Syndrome

Intervention

Drug:
• APL-4098
APL-4098 is administered orally in 28-day cycles
• Azacitidine and APL-4098
Azacitidine is administered at the standard dose of 75mg/m2 on Day 1 - Day 7 of each 28-day cycle; APL-4098 is administered orally.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Apollo Therapeutics Ltd

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Treatment Emergent Adverse Events [Safety] (Phase 1)	Evaluation of safety parameters including treatment emergent adverse events as detected by hematology, chemistry, coagulation safety labs, physical exams, vital signs, Electrocardiogram results	Through study completion, approximately one year
Primary	Incidence of Dose Limiting Toxicities [Tolerability] (Phase 1)	Evaluation of tolerability parameters including dose limiting toxicities as detected by hematology, chemistry, coagulation safety labs, physical exams, vital signs, and Electrocardiogram results	Cycle 1 Day 1 to Cycle 2 Day 1 (a cycle is 28 days)
Primary	Estimate the Maximum Tolerated Dose (MTD) of APL-4098 alone and/or in combination with azacitidine (Phase 1)		Cycle 1 Day 1 to Cycle 2 Day 1 (a cycle is 28 days)
Primary	Determine Recommended Phase 2 Dose (RP2D) levels of APL-4098 alone and/or in combination with azacitidine (Phase 1)		Approximately one year
Primary	Assess the Pharmacokinetics of APL-4098 alone and/or in combination with azacitidine (Phase 1)	Evaluate PK parameters: Maximum plasma concentration (Cmax)	On Days 1, 2, 4, 8, and 15 of Cycle 1, and on Day 1 of Cycle 2 (each cycle is 28 days)
Primary	Assess the Pharmacokinetics of APL-4098 alone and/or in combination with azacitidine (Phase 1)	Evaluate PK parameters: area under the curve (AUC)	On Days 1, 2, 4, 8, and 15 of Cycle 1, and on Day 1 of Cycle 2 (each cycle is 28 days)
Primary	Assess the Pharmacokinetics of APL-4098 alone and/or in combination with azacitidine (Phase 1)	Evaluate PK parameters: Time to peak concentration (Tmax)	On Days 1, 2, 4, 8, and 15 of Cycle 1, and on Day 1 of Cycle 2 (each cycle is 28 days)
Primary	Assess efficacy of APL-4098 alone and/or in combination with azacitidine (Phase 2)	Response is assessed per European LeukemiaNet 2022 criteria	Response is assessed at Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 7 Day 1 (each cycle is 28 days long), then every three cycles thereafter (assessed for up to 2 years)
Secondary	Assess response to disease with APL-4098 alone and/or in combination with azacitidine (Phase 1)	R/R AML and MDS/AML participants: response is assessed per European LeukemiaNet (ELN) 2022 criteria MDS-EB participants: response is assessed per revised International Working Group 2023 response criteria	Response is assessed at Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 7 Day 1 (each cycle is 28 days long), then every three cycles thereafter (assessed for up to 2 years)
Secondary	Duration of response with APL-4098 alone and/or in combination with azacitidine [Further efficacy] (Phase 2)		From Cycle 1 Day 1 (a cycle is 28 days long) through end of study (approximately 2 years)
Secondary	Time to response with APL-4098 alone and/or in combination with azacitidine [Further efficacy] (Phase 2)		From Cycle 1 Day 1 (a cycle is 28 days long) through end of study (approximately 2 years)
Secondary	Event Free Survival with APL-4098 alone and/or in combination with azacitidine [Further efficacy] (Phase 2)		From Cycle 1 Day 1 (a cycle is 28 days long) through end of study (approximately 2 years)
Secondary	Overall Survival with APL-4098 alone and/or in combination with azacitidine [Further efficacy] (Phase 2)		From Cycle 1 Day 1 (a cycle is 28 days long) through end of study (approximately 2 years)
Secondary	Incidence of Treatment Emergent Adverse Events [Further Safety] (Phase 2)	Evaluation of safety parameters including treatment emergent adverse events as detected by hematology, chemistry, coagulation safety labs, physical exams, vital signs, Electrocardiogram results	Through study completion (approximately 2 years)
Secondary	Incidence of Adverse Events leading to discontinuation of APL-4098 [Further Tolerability] (Phase 2)		Through study completion (approximately 2 years)
Secondary	Further assess the PK of APL-4098 alone and/or in combination with azacitidine (Phase 2)	Evaluate PK parameters: Maximum plasma concentration (Cmax)	At Cycle 1 Day 1 and at Cycle 2 Day 1 (each cycle is 28 days)
Secondary	Further assess the PK of APL-4098 alone and/or in combination with azacitidine (Phase 2)	Evaluate PK parameters: area under the curve (AUC)	At Cycle 1 Day 1 and at Cycle 2 Day 1 (each cycle is 28 days)
Secondary	Further assess the PK of APL-4098 alone and/or in combination with azacitidine (Phase 2)	Evaluate PK parameters: Time to peak concentration (Tmax)	At Cycle 1 Day 1 and at Cycle 2 Day 1 (each cycle is 28 days)